rDromaserpin: A Novel Anti-Hemostatic Serpin, from the Salivary Glands of the Hard Tick Hyalomma dromedarii

Hemostatic disorders are caused either by platelet-related dysfunctions, defective blood coagulation, or by a combination of both, leading to an increased susceptibility to cardiovascular diseases (CVD) and other related illnesses. The unique specificity of anticoagulants from hematophagous arthropods, such as ticks, suggests that tick saliva holds great promise for discovering new treatments for these life-threatening diseases. In this study, we combined in silico and in vitro analyses to characterize the first recombinant serpin, herein called Dromaserpin, from the sialotranscriptome of the Hyalomma dromedarii tick. Our in silico data described Dromaserpin as a secreted protein of ~43 kDa with high similarities to previously characterized inhibitory serpins. The recombinant protein (rDromaserpin) was obtained as a well-structured monomer, which was tested using global blood coagulation and platelet aggregation assays. With this approach, we confirmed rDromaserpin anticoagulant activity as it significantly delayed plasma clotting in activated partial thromboplastin time and thrombin time assays. The profiling of proteolytic activity shows its capacity to inhibit thrombin in the micromolar range (0.2 to 1 μM) and in the presence of heparin this inhibition was clearly increased. It was also able to inhibit Kallikrein, FXIa and slightly FXIIa, with no significant effect on other factors. In addition, the rDromaserpin inhibited thrombin-induced platelet aggregation. Taken together, our data suggest that rDromaserpin deserves to be further investigated as a potential candidate for developing therapeutic compounds targeting disorders related to blood clotting and/or platelet aggregation.

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The Antithrombotic Effect of Borneol Related to Its Anticoagulant Property

The American Journal of Chinese Medicine ◽

10.1142/s0192415x08006181 ◽

2008 ◽

Vol 36 (04) ◽

pp. 719-727 ◽

Cited By ~ 23

Author(s):

Yan-Hong Li ◽

Xiao-Ping Sun ◽

Yin-Qing Zhang ◽

Ning-Sheng Wang

Keyword(s):

Platelet Aggregation ◽

Fibrinolytic Activity ◽

Ex Vivo ◽

Anticoagulant Activity ◽

Thrombin Time ◽

Inhibitory Effects ◽

Antithrombotic Activity ◽

Coagulation Parameters ◽

Venous Shunt

Borneol is consumed excessively in China and Southeast Asian countries particularly in combined formula for preventing cardiovascular disease, but few studies were conducted on its effects on thrombosis. In this study, the antithrombotic and antiplatelet activities of borneol were investigated on thrombosis in vivo and on platelet aggregation ex-vivo. In addition, the coagulation parameters and influence on fibrinolytic activity were also assessed. The results showed that borneol had concentration dependent inhibitory effects on arterio-venous shunt and venous thrombosis but no effect on ADP and AA-induced platelet aggregation. Meanwhile, borneol prolonged the coagulation parameters for prothrombin time (PT) and thrombin time (TT), but did not show any fibrinolytic activity. It suggested that the antithrombotic activity of borneol and its action in combined formula for preventing cardiovascular diseases might be due to anticoagulant activity rather than antiplatelet activity.

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The effects of fructose diphosphate on routine coagulation tests in vitro

Scientific Reports ◽

10.1038/s41598-021-04263-y ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Tongqing Chen ◽

Duan Chen ◽

Lu Chen ◽

Zhengxu Chen ◽

Baolong Wang ◽

...

Keyword(s):

Platelet Aggregation ◽

Blood Coagulation ◽

Detection System ◽

Coagulation System ◽

Thrombin Time ◽

Aggregation Rate ◽

Coagulation Testing ◽

Coagulation Tests ◽

Routine Coagulation

AbstractTo evaluate the effects of fructose diphosphate (FDP) on routine coagulation tests in vitro, we added FDP into the mixed normal plasma to obtain the final concentration of 0, 1, 2, 3, 4, 5, 6, 10, 15, 20, 25, 30 and 35 mg/mL of drug. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen (FBG) and thrombin time (TT) of samples were analyzed with blood coagulation analyzers from four different manufacturers(Sysmex, Stago, SEKISUI and Werfen) and their corresponding reagents, respectively. Before the experiment, we also observed whether there were significant differences in coagulation test results of different lots of reagents produced by each manufacturer. At the same time as the four routine clotting tests, the Sysmex blood coagulation analyzer and its proprietary analysis software were used to detect the change of maximum platelet aggregation rate in platelet-rich plasma after adding FDP (0, 1, 2, 3, 4, 5 and 6 mg/mL). The results of PT, aPTT and TT showed a FDP (0–35 mg/mL) concentration-dependent increase and a FBG concentration-dependent decrease. The degree of change (increase or decrease) varied depending on the assay system, with PT and aPTT being more affected by the Sysmex blood coagulation testing instrument reagent system and less affected by CEKISUI, TT less affected by CEKISUI and more affected by Stago, and FBG less affected by Stago and more affected by Sysmex. The results of PT, aPTT and TT were statistically positively correlated with their FDP concentrations, while FBG was negatively correlated. The correlation coefficients between FDP and the coagulation testing systems of Sysmex, Stago, Werfen and SEKISUI were 0.975, 0.988, 0.967, 0.986 for PT, and 0.993, 0.989, 0.990 and 0.962 for aPTT, 0.994, 0.960, 0.977 and 0.982 for TT, − 0.990, − 0.983, − 0.989 and − 0.954 for FBG, respectively. Different concentrations of FDP (0, 1, 2, 3, 4, 5 and 6 mg/mL) had different effects on the maximum aggregation rate of platelet induced by the agonists of adenosine diphosphate (ADP, 5 µmol/L), arachidonic acid (Ara, 1 mmol/L), collagen (Col, 2.5 µg/mL) and epinephrine (Epi,10 µmol/L), but the overall downward trend was consistent, that is, with the increase of FDP concentration, the platelet aggregation rate decreased significantly. Our experimental study demonstrated a possible effect of FDP on the assays of coagulation and Platelet aggregation, which may arise because the drug interferes with the coagulation and platelet aggregation detection system, or it may affect our in vivo coagulation system and Platelet aggregation function, the real mechanism of which remains to be further verified and studied.

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Comparative Studies on An Anti-Xa Enriched Ultra Low Molecular Weight Heparin with Bemiparin

Blood ◽

10.1182/blood.v116.21.4394.4394 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4394-4394

Author(s):

Debra Hoppensteadt ◽

Angel Gray ◽

Josephine Cunanan ◽

Walter Jeske ◽

Jeanine M. Walenga ◽

...

Keyword(s):

Molecular Weight ◽

Platelet Aggregation ◽

Whole Blood ◽

Anticoagulant Activity ◽

The Other ◽

Positive Interactions ◽

Low Molecular Weight ◽

Significant Activity ◽

Thrombin Time ◽

Low Molecular Weight Heparins

Abstract Abstract 4394 Most low molecular weight heparins (LMWHs) have a mean molecular weight in the range of 4–6 kDa and anti-Xa/IIa ratios of 3–6. Further depolymerization of porcine mucosal heparin results in the generation of Ultra low molecular weight heparins (ULMWHs) with a molecular weight range of 2–4 kDa with proportionately decreased anti-Xa and anti-IIa activities. Bemiparin (Rovi, Madrid, Spain) represents one such ULMWH. AVE 5026 (Sanofi-Aventis, Paris, France) is a unique ULMWH (2.5 kDa) which exhibits higher affinity to antithrombin (AT) and therefore, enhanced anti-Xa activity. Because of the compositional differences between these two agents, it was hypothesized that each of these agents will have distinct anticoagulant, antiprotease and thrombin generation effects. Each of these agents was supplemented to native whole blood. Anticoagulant activity was measured using ACT, TEG, PT, APTT, thrombin time and Heptest assays. Similar studies were carried out in plasma. Amidolytic assays were used to determine the anti-Xa and anti-IIa activities. Both agents were also tested for the interactions with heparin cofactor II (HC II) and AT and were compared in the HIT antibody screening assay using platelet aggregation. In whole blood clotting assays bemiparin showed a strong anticoagulant activity in comparison to AVE 5026. Both agents also exhibited assay dependent differences in the APTT, heptest and thrombin time assays. AVE 5026 exhibited a higher anticoagulant activity in the heptest whereas bemiparin showed a stronger anticoagulant effect in the other clot based assays. In the amidolytic anti-Xa assay, AVE 5026 showed an activity of 156U/mg compared to 86 U/mg for bemiparin. In the anti-IIa assay bemiparin showed a higher activity (10 U/mg) in comparison to AVE 5026 (3.2 U/mg). The calculated Xa/IIa ratio of AVE 5026 was > 48, whereas it was 8.6 for bemiparin. While bemiparin exhibited interactions with HC II, AVE 5026 did not show significant activity in the tested concentrations (anti-IIa – IC50: 1.10±.45 μ M and >3.44±.00 μ M, respectively). On the other hand, AVE 5026 exhibited stronger interactions with AT in comparison to bemiparin (anti-FXA – IC50: .223±.03 μ M and .894±.06 μ M, respectively). Interestingly, heparinase digestion of the two products resulted in a complete loss of anti-IIa activity, but residual anti-Xa activity was found. AVE 5026 exhibited stronger anti-Xa interactions even after heparinase digestion. In the heparin induced platelet aggregation assay at 2.5 μ g/ml, bemiparin showed a relatively higher prevalence of positive interactions with HIT antibodies, whereas AVE 5026 showed a much lower prevalence (slope; AVE 5026 compared bemiparin, p=0.012). Bemiparin exhibited greater platelet factor 4 neutralization in comparison to AVE 5026. These studies clearly demonstrate that while bemiparin behaves like a typical ULMWH, AVE 5026 behaves differently in the different assays. Moreover, the oligosaccharide composition of the two products, in terms of distribution profile structure, is also different. Therefore, AVE 5026 does not represent a typical depolymerized ULMWH and is expected to exhibit a distinct pharmacologic and clinical profile. Disclosures: Hoppensteadt: Sanofi-Aventis: Research Funding.

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Anti-Heparin and Platelet Aggregation Activities of Polyamino Acids

10.1055/s-0039-1680801 ◽

1977 ◽

Author(s):

Jawed Fareed ◽

Harry L. Messmore ◽

John U. Balis ◽

Rogelio Moncada

Keyword(s):

Platelet Aggregation ◽

Contrast Media ◽

Platelet Rich Plasma ◽

Anticoagulant Activity ◽

Lag Time ◽

Thrombin Time ◽

Irreversible Aggregation ◽

Induced Aggregation ◽

Aggregation Of Platelets ◽

Biphasic Process

An earlier report from this laboratory has described the antagonism of the anticoagulant effect of heparin by certain basic polyamino acids. Of the numerous polyamino acids tested, only basic polyarnino acids such as poly-L-lysine (MW 85,000) and poly-L-omithine (MW 120,000) effectively neutralized heparinized plasma (1 u/ml) in concentrations less than 10 μg/ml. Addition of these two polyamino acids in quantities up to 50 μg/ml citrated plasma, significantly shortened the thrombin time. Poly-L-proline (MW 19,000), poly-L-histidine (MW 16,000) and poly-L-lysine (MW 85,000) possessed weak anti-heparin action. These polyamino acids also neutralized the anticoagulant activity of hirudin and polyanetholsulfonic acid in varying degrees. The effects of polyamino acids on platelet aggregation was also tested. Of the 15 basic polyamino acids tested, only poly-L-α-omithine was found to induce aggregation of platelets. Polyornithine in the amounts of 50.0, 25.0 and 12.5 μg/ml to platelet rich plasma caused a 65, 45 and 30% change in transmittance, respectively. The polyornithine induced aggregation (PIA) of platelets was only partially blocked by acetylsalicylic acid. Contrast media (6.0 mg/ml) used in diagnostic radiology and meglumine (5 mg/ml) totally blocked the PIA. The PIA of platelets was found to be a biphasic process, an initial lag time of 30 seconds, after which irreversible aggregation was observed. These studies suggest that basic polyamino acids may be used clinically to antagonize overheparinization; in addition, polyornithine may prove useful in the diagnosis of platelet function defects.

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Anticoagulant Activity of Hirulog™, a Direct Thrombin Inhibitor, in Humans

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651573 ◽

1993 ◽

Vol 69 (02) ◽

pp. 157-163 ◽

Cited By ~ 137

Author(s):

Irving Fox ◽

Adrian Dawson ◽

Peter Loynds ◽

Jane Eisner ◽

Kathleen Findlen ◽

...

Keyword(s):

Rational Design ◽

Therapeutic Potential ◽

Anticoagulant Activity ◽

Subcutaneous Administration ◽

Direct Thrombin Inhibitor ◽

Controlled Study ◽

Thrombin Inhibitor ◽

Thrombin Time ◽

Thrombotic Disease ◽

Dose Dependent

SummaryHirulog™ (BG8967) is a direct thrombin inhibitor built by rational design using the protein hirudin as a model (Maraganore et al. [1990]; Biochemistry 29: 7095–101). In order to evaluate the therapeutic potential for hirulog in the management of thrombotic disease, the tolerability and anticoagulant activity of the agent were examined in a study of human volunteers.In a randomized, placebo-controlled study (n = 54), the intravenous infusion of hirulog over 15 min showed a rapid, dose-dependent prolongation of activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). There was a corresponding dose-dependent increase in plasma hirulog levels. The peptide was rapidly cleared with a half-life of 36 min and a total body clearance rate for the peptide of 0.43 1 kg−1 h−1. Similar activity was observed following subcutaneous injection but with sustained pharmacodynamic and pharmacokinetic behavior. There was a significant correlation between pharmacokinetic and pharmacodynamic variables for both intravenous (r = 0.8, p <0.001) and subcutaneous administration (r = 0.7, p = 0.002).To evaluate the possible interactions of aspirin on the tolerability and anticoagulant activity of intravenous hirulog, a cross-over design was employed in eight subjects. Aspirin administration did not modify the peptide’s activity. At the administered dose of 0.6 mg kg−1 h−1 for 2 h, hirulog infusion prolonged APTT from 230 to 260% baseline. The infusion of hirulog in subjects who had received aspirin was not associated with any significant changes in the template bleeding time.The final phase of the study examined the activity and tolerability of hirulog in ten subjects during prolonged intravenous infusions for up to 24 h. The peptide (0.3 mg kg−1 h−1) exhibited sustained anticoagulant activity with no evidence for a cumulative effect. During hirulog infusion, APTT was prolonged from 210 to 250% baseline.In all phases of the study, hirulog administration was generally well-tolerated.Our observations show that hirulog is an active antithrombin agent with excellent tolerability in humans. As a direct thrombin inhibitor, hirulog provides a novel approach for the management of thrombotic disease.

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Mechanism of Inhibitory Action on Platelet Activation of a Phospholipase A2 Isolated from Lachesis muta (Bushmaster) Snake Venom

Thrombosis and Haemostasis ◽

10.1055/s-0038-1665414 ◽

1997 ◽

Vol 78 (05) ◽

pp. 1372-1380 ◽

Cited By ~ 56

Author(s):

André L Fuly ◽

Olga L T Machado ◽

Elias W Alves ◽

Célia R Carlinis

Keyword(s):

Platelet Aggregation ◽

Enzymatic Activity ◽

Phospholipase A2 ◽

Inhibitory Activity ◽

Thermal Inactivation ◽

Anticoagulant Activity ◽

Gel Filtration ◽

Apparent Molecular Weight ◽

Crude Venom ◽

Lachesis Muta

SummaryCrude venom from Lachesis muta exhibited procoagulant, proteolytic and phospholipase A2 activities. A phospholipase A2, denoted LM-PLA2 was purified from L. muta venom to homogeneity, through a combination of chromatographic steps involving gel-filtration on Sephacryl S-200 HR and reverse phase chromatography on a C2/C18 column. LM-PLA2 presented a single polypeptide chain with an isoelectric point at pH 4.7 and apparent molecular weight of 17 kDa. Partial aminoacid sequence indicated a high degree of homology for LM-PLA2 with other PLA2 from different sources.LM-PLA2 displayed a potent enzymatic activity as measured by indirect hemolysis of red blood cells but it was neither lethal when injected i.p. into mice nor did it present anticoagulant activity. Furthermore, LM-PLA2 displayed a moderate inhibitory activity on the aggregation of rabbit platelets induced by low levels of ADP, thrombin and arachidonate. In contrast, platelet aggregation induced by high doses of collagen was strongly inhibited by LM-PLA2 as well as ATP-release. Treatment of the protein with p-bromophenacyl bromide or 2-mercapto-ethanol, as well as thermal inactivation studies, suggested that the platelet inhibitory effect of LM-PLA2 is dependent on its enzymatic activity. Thus, the platelet inhibitory activity of LM-PLA2 was shown to be dependent on the hydrolysis of plasma phospholipids and/or lipoproteins, most probably those rich in phosphatidylcholine. Surprisingly, lyso-phosphatidylcholine released by LM-PLA2 from plasma was shown to preferentially inhibited collagen-induced platelet aggregation, in contrast to other PLA2s, whose plasma hydrolytic products indistinctly affect platelet’s response to several agonists.

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International Quality Control In Blood Coagulation: Measurement Of Fibrinogen

10.1055/s-0038-1665656 ◽

1979 ◽

Author(s):

Jean Thomson ◽

L Poller ◽

K Yee

Keyword(s):

Quality Control ◽

Blood Coagulation ◽

Thrombin Time

Fibrinogen estimations were included in four of the collaborative exercises from the above Centre between 1976-1978. More than thirty different techniques were employed by participants in over four hundred laboratories. The thrombin time, fibrinogen titre and turbidity techniques showed poor discrimination between normal and low fibrinogen levels compared with other routine methods e.g. Clauss technique, immunological and clot weight methods.

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EFFECTS OF NICKEL CHLORIDE ON INDICES OF HEMOCOAGULATION AND LIPID PEROXIDATION IN RATS

ZHurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia» ◽

10.25557/0031-2991.2019.01.83-90 ◽

2019 ◽

pp. 83-90

Author(s):

Э.М. Гаглоева ◽

В.Б. Брин ◽

С.В. Скупневский ◽

Н.В. Боциева ◽

Т.В. Молдован

Keyword(s):

Lipid Peroxidation ◽

Antioxidant Enzymes ◽

Platelet Aggregation ◽

Prothrombin Time ◽

Partial Thromboplastin Time ◽

Nickel Chloride ◽

Activated Partial Thromboplastin Time ◽

Fibrinogen Concentration ◽

Thrombin Time ◽

Hemostasis System

Цель исследования - изучить состояние системы гемостаза при хронической интоксикации хлоридом никеля, исследовать взаимосвязь показателей гемокоагуляции с процессами липопероксидации у крыс в эксперименте. Методика. Опыты проводили на крысах-самцах Вистар (n=50, 230-250 г). Раствор NiCl2 (5 мг/кг) вводили внутрижелудочно ежедневно в течение 2 нед, 1 и 2 мес. По завершении эксперимента исследовали состояние тромбоцитарного и коагуляционного звеньев гемостаза, антикоагулянтную и фибринолитическую активность крови, а также определяли активность процессов перекисного окисления липидов и антиоксидантных ферментов. Результаты. Установлено, что через 2 нед и 1 мес интоксикации у крыс отмечались гиперкоагуляционные изменения показателей свертывающей системы крови: повышение агрегационной активности тромбоцитов, увеличение концентрации фибриногена, снижение активированного частичного тромбопластинового времени (АЧТВ) и протромбинового времени. В этот период регистрировалось увеличение антитромбиновой и фибринолитической активности крови. Через 2 мес наблюдалось подавление активности клеточного звена гемостаза - тромбоцитопения, ослабление степени АДФ-индуцируемой агрегации тромбоцитов. Выявлялась тенденция к уменьшению концентрации фибриногена. На фоне снижения АЧТВ и тромбинового времени отмечалось увеличение протромбинового времени. В то же время регистрировалось угнетение противосвертывающего звена системы гемостаза (снижалась активность антитромбина III), наблюдалось истощение резервных возможностей фибринолитического звена (замедление фXIIа-зависимого эуглобулинового лизиса) и увеличение содержания растворимых фибрин мономерных комплексов, что свидетельствует о наличии тромбинемии. Через 2 нед, один и два месяца интоксикации у животных выявлялись корреляционные связи между основными показателями системы гемостаза и активностью процессов перекисного окисления липидов и антиоксидантных ферментов. Заключение. Полученные данные подтверждают наличие взаимосвязи активности процессов липопероксидации и системы гемостаза, в том числе при хронической никелевой интоксикации. Результаты исследования позволяют рекомендовать применение антиоксидантов для разработки способов коррекции гемостатических сдвигов при воздействии на организм тяжелых металлов. The aim. To study the state of the hemostasis system in chronic nickel intoxication and to investigate the relationship between hemocoagulation indices and lipoperoxidation processes in rats. Methods. Experiments were carried out on male Wistar rats (n=50, 230-250 g). A solution of nickel chloride (5 mg/kg) was administered daily intragastrically for two weeks, one and two months. At the end of the experiments, indices of platelet and coagulation hemostasis systems, anticoagulant and fibrinolytic activity of blood plasma, and activities of lipid peroxidation and antioxidant enzymes were studied. Results. Hypercoagulative changes in indices of the coagulation system were observed in rats after two weeks and one month of intoxication, including increased platelet aggregation and fibrinogen concentration and shortened activated partial thromboplastin time and prothrombin time. During the same period, increased antithrombin and fibrinolytic activities were observed. The depressed activity of the cellular component of hemostasis evident as thrombocytopenia and impaired ADP-induced platelet aggregation was detected after two months of intoxication. A tendency to decrease in fibrinogen concentration was observed. The shortened activated partial thromboplastin time and thrombin time were associated with prolonged prothrombin time. At the same time, inhibition of the anticoagulant component of hemostasis (decreased antithrombin III activity), exhaustion of the fibrinolysis system reserve (delayed fXIIa-dependent euglobulin lysis), and a significant increase in soluble fibrin monomeric complexes indicative of thrombinemia were observed. After two weeks, one and two months of nickel intoxication, a correlation was found between the major indices of the hemostasis system and the activities of lipid peroxidation and antioxidant enzymes. Conclusion. The study confirmed a relationship between the lipid peroxidation activity and the hemostasis system, specifically in chronic nickel intoxication. This result allows to recommend the use of antioxidants in developing methods for correction of hemostatic induced affected by heavy metals.

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Study of Haemostasis in Schoenlein-Henoch’s Syndrome

10.1055/s-0039-1689507 ◽

1975 ◽

Cited By ~ 1

Author(s):

Gy. Boros ◽

J. Sámik ◽

Ljubov Gofman ◽

Judit Nagv ◽

Gy. Deák ◽

...

Keyword(s):

Electron Microscopy ◽

Light Microscopy ◽

Blood Coagulation ◽

Fibrinolytic Activity ◽

Capillary Permeability ◽

Thrombin Time ◽

Consumption Coagulopathy ◽

Fibrin Deposition ◽

Coagulation Defect ◽

Capillary Resistance

Blood coagulation, thrombocyte function and capillary resistance were studied in 21 adult patients with Schoenlein-Henoch’s syndrome. 20 different tests were carried out at different stages of the disease. In 2 cases skin, in 1 mesocolon and in 10 kidneys were examined histologicaly (light microscopy, immunofluorescence, electron microscopy).Capillary permeability was increased at least once in every patient. All patients but 2 were characterized by hypercoagulability. In addition to thrombotic changes, an increase in labile fibrinogen was detected in the serum of 12 patients, and thrombin time was prolonged in 11 patients on 31 occasions. Plasma fibrinolytic activity was increased in 11 patients. Fibrin deposition was demonstrable in the skin of 2 in the mesocolon of 1 and in the kidneys of 7 patients.It is suggested that besides the capillaropathy a coagulation defect, resembling consumption coagulopathy is a characteristic of Schoenlein-Henoch’s syndrome.

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Antihemostatic Effect of Hsien-Ho-T'sao (Agrimonia pilosa)

The American Journal of Chinese Medicine ◽

10.1142/s0192415x8400012x ◽

1984 ◽

Vol 12 (01n04) ◽

pp. 116-123 ◽

Cited By ~ 9

Author(s):

Jih-Pyang Wang ◽

Mei-Feng Hsu ◽

Che-Ming Teng

Keyword(s):

Prothrombin Time ◽

Blood Coagulation ◽

Partial Thromboplastin Time ◽

Bleeding Time ◽

Fibrinogen Level ◽

Platelet Rich Plasma ◽

Water Extract ◽

Activated Partial Thromboplastin Time ◽

Thrombin Time

Bleeding time in rats was markedly prolonged after the adminstration of the water extract of Hsien-Ho-T'sao. This antihemostatic effect was more marked in the group of i.p. injection of the drug than in the group of p.o. administration for 2 to 7 consecutive days. Blood coagulation studies showed that plasma prothrombin time, activated partial thromboplastin time and stypven time were prolonged, while thrombin time adnd fibrinogen level were not changed. The thromboelastographic recording showed that reation time was prolonged and maximal elasticity of clot was decreased. In addition, ADP- and collagen- induced aggregations of platelet-rich plasma was suppressed. In conclusion, the prolongation of the bleeding time might be due to both anticoagulant and antiplatelet action of the drug.

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